Skeletal manifestations of lysinuric protein intolerance

Abstract

Lysinuric protein intolerance (LPI) is an autosomal recessive disease caused by defective transport of the cationic amino acids lysine, arginine, and ornithine at the cell membrane. About 80 patients with LPI have been described worldwide, almost half of them in Finland. The symptoms appear in early childhood as a failure to thrive, growth retardation, muscular hypotonia, and episodes of stupor after protein-rich meals. Twenty-nine Finnish patients (current median age 24.8 years, range 3.7-47.9 years) over a mean follow-up time of 18.1 years (range 1.2-27.2 years) had 57 fractures after minor trauma, mostly in childhood. Their 440 skeletal radiographs showed severe osteoporosis (13/29), controversially abnormal thickening of cortex of the metacarpals (7/29), or thin cortices of the long bones (5/29), endplate impression of vertebrae (8/29), rickets-like metaphyses (2/29), or early destruction of cartilage (3/29). Skeletal maturation was delayed by 1-5 years in 23 of 24 patients. There was no correlation between fracture incidence, radiological bone structure, and delayed skeletal maturation.

Bone Marrow Hemophagocytosis and Immunological Abnormalities in a Patient with Lysinuric Protein Intolerance

“…However, any organ system can be affected, and the patients may present with one or more of the symptoms related to pulmonary, renal, pancreatic, hematologic, mus culoskeletal and neurological involvement [8][9][10][11][12], Hema tological abnormalities include hemolytic anemia, throm bocytopenia and hemophagocytosis in the bone marrow. The most frequent bone marrow abnormality is reported to be erythroblastophagocytosis which is observed in the ma jority of Italian patients, all of whom originate from the Southern part of the country [3,4], and in a Turkish patient [ 13] but is not encountered in Finnish patients whose bone marrow was examined [9,11],…”

Long-term oral lysine supplementation in lysinuric protein intolerance

“…Most patients have structural abnormalities in the skeleton, but there is no correlation between fracture incidence and radiologic bone structure [17]. The patients do not usually show clinical or biochemical signs of rickets.…”

Hazards associated with pregnancies and deliveries in lysinuric protein intolerance

“…Serum calcium concentration decreased during pregnancy in almost all LPI pregnancies, and 3 of 7 patients had serum calcium concentration below the reference range at the third trimester. In patients with LPI, the concentrations of serum calcium and phosphate are usually within reference ranges, but severe osteoporosis is common, and the patients have a pronounced tendency to have fractures especially in childhood [29]. Although the mothers obviously had poor calcium stores, none of the children developed hypocalcemia.…”